– Our understanding of HIV pathogenesis and standards of clinical care has changed greatly over the last several years, the following examples represent our current understanding of the disease and its treatment

(1) Viral Turnover

: HIV turns over at a rate of ~10billion/day in the steady state; the implication is that due to the high mutation rate of the virus, every viable mutation is present and replicating in each host each day

(2)

Clearance from the Plasma: HAART therapy results in two phases of viral decay

Þ rapid decay of activated HIV+ CD4+ cells; slower decay (probably due to death of less active HIV+ CD4+ cells)

(3) Latently Infected Cells

: infection of inactive memory T cells has recently been demonstrated; HIV provirus is contained in less than 1/1M cells, but these proviri are resistant to HAART

(4) Immune Defenses against HIV

: acute infection initially results in high levels of virus which later fall to a ‘set point’ that is an important predictor of long-term prognosis; this initial drop in viral levels is most likely mediated by:

CD4+ cells: initially active in immune response, but activity falls rapidly; this CD4+ response in maintained in long-term non-progressors, and also in patients who receive HAART early during acute HIV infection syndrome

(5) Immune Restoration after HAART

: some restoration occurs, evidenced by decreased opportunisitic infections after HAART; occurs in two phases Þ first: non-specific increase in naïve CD4+, CD8+, and memory cells; second: increase in CD4+ and CD8+ cells that continues in the first year of therapy (may represent normalizing of the T cell repertoire)

(6) Role of the General Internist in HIV management

: experience of the physician with HIV is a major determinant in survival, so only docs whose main practice is HIV should be treating these patients (example: improper treatment with antivirals can render a patient resistant to the entire class); GPs can do some things Þ